Key result
P-P-8P effectively delivered the antioxidant peptide 8P to cardiomyocytes, preventing oxidative stress in vitro and protecting against doxorubicin-induced cardiac dysfunction in mice.
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Why the study?
Doxorubicin has significant cardiotoxicity linked to oxidative stress, leading researchers to explore whether cardiomyocyte-targeted liposomal delivery of the antioxidant peptide 8P can prevent doxorubicin-induced cardiac injury.
Does P-P-8P prevent doxorubicin-induced myocardial injury in preclinical models?
Does P-P-8P prevent doxorubicin-induced myocardial injury in preclinical models?
Myocardium-targeted liposomal delivery of the antioxidant peptide 8P protects against doxorubicin-induced cardiotoxicity in preclinical models.
8P attenuates doxorubicin oxidative injury in vitro; hypothesis-generating for clinical cardioprotection.
Doxorubicin (Dox) is a broad-spectrum antineoplastic chemotherapeutic agent used in clinical settings, yet it exhibits significant cardiotoxicity, which in severe cases can lead to heart failure. Research indicates that oxidative stress plays a pivotal role in Dox -induced cardiomyocyte injury. Therefore, the application of antioxidants represents an effective strategy to mitigate the cardiotoxic effects of doxorubicin. In preliminary studies, we isolated an antioxidative peptide, PHWWEYRR (8P). This study utilizes a PCM cardiomyocyte-targeting peptide-modified liposome as a carrier to deliver 8P into cardiomyocytes, aiming to prevent Dox-induced cardiac injury through its antioxidative mechanism. The results demonstrated that we prepared the 8P-loaded and PCM-targeting peptide-modified liposome (P-P-8P), which exhibited good dispersibility, encapsulation efficiency, drug loading capacity, and in vitro release, along with myocardial targeting capability. In vitro experiments showed that P-P-8P could prevent oxidative stress injury in H9C2 cells, protect mitochondrial functions, and inhibit cell apoptosis through a mitochondria-dependent pathway. In vivo experiments indicated that P-P-8P could prevent abnormalities in serum biochemical indicators, cardiac dysfunction, and myocardial pathological changes in mice. In conclusion, P-P-8P effectively delivers 8P to cardiomyocytes, offering protection against the cardiotoxic effects of Dox, and holds potential as a future preventative or therapeutic agent for drug-induced cardiomyopathy.
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Zhao et al. (2024) studied Doxorubicin-induced myocardial injury. 8P-loaded and PCM-targeting peptide-modified liposome (P-P-8P) was evaluated on Prevention of Dox-induced cardiac injury (oxidative stress, mitochondrial function, apoptosis, cardiac dysfunction). P-P-8P effectively delivered the antioxidant peptide 8P to cardiomyocytes, preventing oxidative stress in vitro and protecting against doxorubicin-induced cardiac dysfunction in mice.
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